High-resolution global peptide-protein docking using fragments-based PIPER-FlexPepDock
High-resolution global peptide-protein docking using fragments-based PIPER-FlexPepDock
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DOI：
10.1371/journal.pcbi.1005905
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发表时间：
2017-12-01
影响因子：
4.3
通讯作者：
Schueler-Furman, Ora
中科院分区：
文献类型：
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作者：
Alam, Nawsad;Goldstein, Oriel;Schueler-Furman, Ora
肽-蛋白质相互作用是蛋白质-蛋白质相互作用组的重要组成部分。由于高度灵活的多肽与大受体表面的相互作用相关的巨大构象空间，这些相互作用的准确建模具有挑战性。为了解决这一挑战，我们开发了一种基于片段的高分辨率肽蛋白对接方案。通过简化用于精确生成肽片段集合的Rosetta片段拾取器、用于详尽片段-受体刚体对接的PIPER对接算法和用于PIPER对接模型的柔性全原子细化的Rosetta FlexPepDock，我们成功地解决了准确高效的高分辨率全局肽蛋白对接的挑战。通过x射线晶体学很好地解析了一小组具有代表性的肽-蛋白复合物结构。我们的方法为更多肽-蛋白质相互作用的高分辨率建模和肽-蛋白质结合的详细研究开辟了道路。PIPER-FlexPepDock作为服务器免费提供给学术界，网址为http://piperfpd。furmanlab.cs.huji.ac.il。
Peptide-protein interactions contribute a significant fraction of the protein-protein interactome. Accurate modeling of these interactions is challenging due to the vast conformational space associated with interactions of highly flexible peptides with large receptor surfaces. To address this challenge we developed a fragment based high-resolution peptide-protein docking protocol. By streamlining the Rosetta fragment picker for accurate peptide fragment ensemble generation, the PIPER docking algorithm for exhaustive fragment-receptor rigidbody docking and Rosetta FlexPepDock for flexible full-atom refinement of PIPER docked models, we successfully addressed the challenge of accurate and efficient global peptideprotein docking at high-resolution with remarkable accuracy, as validated on a small but representative set of peptide-protein complex structures well resolved by X-ray crystallography. Our approach opens up the way to high-resolution modeling of many more peptide-protein interactions and to the detailed study of peptide-protein association in general. PIPER-FlexPepDock is freely available to the academic community as a server at http://piperfpd. furmanlab.cs.huji.ac.il.